• Journal of The Korean Society of Integrative Medicine
• /
• v.11 no.3
• /
• pp.159-169
• /
• 2023

Purpose : Though other Citrus spp. have reported their anti-inflammatory and antioxidative activities in previous studies, the biological activity of Kiyomi (Citrus unshiu × C. sinensis) has not been reported yet. Therefore, this study attempted to analyze the anti-inflammatory mechanisms of Kiyomi leaf ethanol extract (KLEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : The cytotoxic effect of KLEE in RAW 264.7 cells was determined by WST-1 assay. Bacterial endotoxin, the concentration of nitric oxide (NO) was analyzed by the Griess reaction. In addition, Western blot analysis was applied to measure the protein expression level of inducible NO synthase (iNOS). The phosphorylated status of the critical inflammatory transcription factor, nuclear factor (NF)-𝜅B, and its upstream signaling molecules, phosphoinositide 3-kinase (PI3K)/Akt as well as mitogen-activated protein kinases (MAPKs), were also measured by Western blot analysis. Results : KLEE was not cytotoxic up to a concentration of 200 ㎍/㎖, and protein expression levels of iNOS and cyclooxygenase (COX)-2, enzymes that counteract NO and prostaglandin (PG) E2 production, were inhibited by KLEE treatment. The phosphorylated status of PI3K/Akt as well as MAPKs including extracellular regulated kinase (ERK), c-jun NH2kinase (JNK), and p38, were significantly attenuated by KLEE treatment in LPS stimulated RAW 264.7 cells. Moreover, one of phase II enzymes, heme oxygenase (HO)-1 which has known for its anti-inflammatory capacity, was strongly induced by KLEE treatment. Conclusion : Consequently, KLEE treatment significantly attenuated the production of NO as well as the expression levels of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-𝜅B, as well as its upstream signaling molecules, PI3K/Akt and MAPKs, were also diminished by KLEE treatment with statistical significance in LPS-stimulated RAW 264.7 cells. These results suggest that KLEE might be a promising candidate for the attenuation of inflammatory disorders.

• Biomolecules & Therapeutics
• /
• v.14 no.1
• /
• pp.11-18
• /
• 2006

Certain flavonoids possess anti-inflammatory activity. Besides their antioxidative property, the cellular action mechanisms of flavonoids include an inhibition of arachidonate metabolizing enzymes such as cyclooxygenases and lipoxygenases, and a down-regulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-$\alpha$. In this review, the recent findings of anti-inflammatory flavonoid research since 2004 were summarized. And the cellular mechanisms on signal transduction pathways were also discussed.

• Korean Journal of Plant Resources
• /
• v.32 no.6
• /
• pp.669-676
• /
• 2019

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E₂ (PGE₂), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE₂ and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

• Biomedical Science Letters
• /
• v.18 no.4
• /
• pp.338-344
• /
• 2012

Mollugin is the active compound of Rubia cordifolia, a well known herb widely used in alternative medicines for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated the anti-inflammatory effects of mollugin in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Treatment with mollugin significantly inhibited LPS-induced release of nitric oxide, prostaglandin $E_2$, and inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6. In addition, mollugin suppressed LPS-induced nuclear factor-kappa B (NF-${\kappa}B$) transcriptional activity. These results suggest that mollugin inhibits LPS-induced expression of inflammatory molecules via NF-${\kappa}B$, at least in part, and indicate the potential value of mollugin as a valuable new drug candidate for the treatment of various inflammatory diseases.

• Journal of Ginseng Research
• /
• v.39 no.1
• /
• pp.61-68
• /
• 2015

Background: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods: We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results: PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-${\alpha}$, and prostaglandin $E_2$], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-${\alpha}$, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion: These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).

• Journal of Microbiology and Biotechnology
• /
• v.29 no.7
• /
• pp.1022-1032
• /
• 2019

Probiotics are known to provide the host with immune-modulatory effects and are therefore of remarkable interest for therapeutic and prophylactic applications against various disorders, including inflammatory diseases. Weissella cibaria JW15 (JW15) has been reported to possess probiotic and antioxidant properties. However, the effect of JW15 on inflammatory responses has not yet been reported. Therefore, the objective of the current study was to evaluate the anti-inflammatory potential of JW15 against lipopolysaccharide (LPS) stimulation. The production of pro-inflammatory factors and the cellular signaling pathways following treatment with heat-killed JW15 was examined in LPS-induced RAW 264.7 cells. Treatment with heat-killed JW15 decreased nitric oxide and prostaglandin $E_2$ production via down-regulation of the inducible nitric oxide synthase and cyclooxygenase-2. In addition, treatment with heat-killed JW15 suppressed the expression of pro-inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. The anti-inflammatory properties of treating with heat-killed JW15 were associated with mitogen-activated protein kinase signaling pathway-mediated suppression of nuclear factor-${\kappa}B$. These results indicated that JW15 possesses anti-inflammatory potential and provide a molecular basis regarding the development of functional probiotic products.

• The Journal of Korean Medicine
• /
• v.37 no.4
• /
• pp.10-21
• /
• 2016

Objectives: This study was to investigate the anti-oxidative and anti-inflammatory effect of Psoralea corylifolia water extract (PE) on ulcerative colitis which was induced by dextran sulfate sodium (DSS) in mice. Methods: Ulcerative colitis was induced by DSS in male BALB/c mice. The mice were divided into 3 groups. The control group (Ctrl) was not induced ulcerative colitis. The pathological group (CE) was induced the colitis. The experimental group (PT) was administered PE after inducing the colitis. The effects of the PE on ulcerative colitis were evaluated by morphological change in the colon tissue and cells, substance P production, activity of tumor necrosis factor $(TNF)-{\alpha}$ and nuclear factor $(NF)-{\kappa}B$, cyclooxygenase (COX)-2 production, and anti-oxidative activity. Results: In the PT group, PE alleviated hemorrhagic erosion in colon mucosa and infiltration of inflammatory cells in lamina propria mucosae. In the colon of the PT group, COX-2 production was inhibited via regulating the activity of $TNF-{\alpha}$ and $NF-{\kappa}B$ p65. PE also had an anti-oxidative effect via activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Conclusions: In this study, we found the utility of treatment with PE and the potential of developing a medicine for ulcerative colitis by applying our results. Further investigations for the anti-inflammatory mechanism of PE may be needed.

• BMB Reports
• /
• v.44 no.6
• /
• pp.399-404
• /
• 2011

In this study, powder of Orostachys japonicus A. Berger (O. japonicus) was extracted with 95% ethyl alcohol and fractionated using a series of organic solvents, including n-hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n-butanol (BuOH), and water ($H_2O$). We investigated the anti-inflammatory effects of these O. japonicus extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Their effects on the expression of inflammatory mediators and transcription factors were analyzed by Western blotting. DCM fraction significantly inhibited formation of reactive oxygen species (ROS) as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Phosphorylation of the pro-inflammatory transcription factor complex nuclear factor-kappa B (NF-${\kappa}$B) p65 and expression of inducible nitric oxide synthase (iNOS), one of its downstream proteins, were also suppressed by DCM fraction. These effects were regulated by upsteam proteins in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways. Taken together, our data suggest that O. japonicus could be used as a potential source for anti-inflammatory agents.

• Korean Journal of Plant Resources
• /
• v.34 no.6
• /
• pp.503-509
• /
• 2021

Marine sources as potential treatment options for various diseases have been a subject of growing interest. However, information on the anti-inflammatory mechanism employed by Undaria pinnatifida (UP) remains limited. The present study was conducted to investigate the mechanisms of UP on the mast cell-mediated inflammatory response. To determine the pharmacological mechanism of UP in inflammatory reaction, we evaluated the effects of UP on interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α production and nuclear factor-κB (NF-κB) and caspase-1 activation in calcium ionophore A23187 plus phorbol 12-myristate 13-acetate-stimulated human mast cells-1 (HMC-1). The results showed that UP suppressed IL-6, IL-8 and TNF-α production in a dose-dependent manner. Moreover, UP significantly attenuated NF-kB/caspase-1 activation in stimulated HMC-1. Collectively, these findings provide experimental evidence that UP may be a useful candidate for the inflammation-related diseases treatment.

• The Korea Journal of Herbology
• /
• v.33 no.5
• /
• pp.73-79
• /
• 2018

Objectives : Coriandrum sativum is a medicinal herb that is used to enhance organoleptic quality and food flavor and as source of natural antioxidants. This research investigated the anti-inflammatory activity of Coriandrum sativum stem methanol extract (CSSE) using RAW 264.7 cells. Methods : Production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and nitric oxide (NO) in the culture supernatant, protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-${\kappa}B$) in the extract were assayed. Results : Treatment with CSSE ($100{\mu}g/m{\ell}$) resulted in inhibited levels of protein expression of lipopolysaccharide- (LPS-) induced iNOS, COX-2, and NF-${\kappa}B$ as well as production of TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and NO induced by LPS. Conclusions : These results demonstrate that CSSE exhibits anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the pathways of NF-${\kappa}B$ in LPS-induced RAW 264.7 cells. Thus, CSSE may have therapeutic potential for a variety of inflammation-mediated diseases.